Background Cytokine storm observed in patients with severe Coronavirus Disease 2019 (COVID-19) contributes to poor clinical outcomes and increased mortality. Janus kinases (JAKs) are important mediators in the cytokine storm. Therefore, we conduct a living systematic review and meta-analysis of the literature investigating efficacy and safety of JAK inhibitors for patients with COVID-19. Methods Databases were searched up to December 1, 2021 for interventional and observational studies comparing JAK inhibitor treatment with concurrent control in patients with COVID-19. Efficacy and safety outcomes were evaluated by pooled risk ratio (RR). Results Of 3,170 records retrieved, 15 studies were eligible and 13 were evaluated in the meta-analysis ( n = 3,977). Based on data from three randomized controlled trials (RCTs), baricitinib treatment significantly decreased mortality by day 28 in hospitalized patients with COVID-19 (RR = 0.64, 95% CI 0.51–0.80) without increasing the incidence of adverse outcomes. In subgroup analysis, patients who required supplemental oxygen (RR = 0.62, 95% CI 0.41–0.95) or high-flow oxygen/non-invasive ventilation (RR = 0.59, 95% CI 0.42–0.85) at baseline benefited most. Pooled analysis of all eligible studies for JAK inhibitors (baricitinib, ruxolitinib, tofacitinib, and nezulcitinib) demonstrated a significant decrease in mortality (RR = 0.62, 95% CI 0.49–0.78) with no increase in the risk of adverse events. Conclusion Baricitinib probably decreases mortality in hospitalized adult patients with COVID-19, especially for patients who required supplemental oxygen or high-flow oxygen/non-invasive ventilation at baseline. The efficacy and safety of other JAK inhibitors, such as ruxolitinib, tofacitinib, and nezulcitinib, await more evidence. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021261414 , identifier: CRD42021261414.
【저자키워드】 COVID-19, Meta-analysis, SARS-CoV-2, Baricitinib, systematic review, Janus kinase inhibitors, 【초록키워드】 Randomized controlled trial, Treatment, review, Hospitalized, Mortality, Ventilation, risk, outcome, database, observational study, adverse outcomes, Clinical outcome, adverse events, Registration, Patient, ruxolitinib, Efficacy and safety, jak inhibitors, incidence, JAK inhibitor, RCTs, Evidence, Tofacitinib, Janus kinase, Analysis, supplemental oxygen, 95% CI, decreased mortality, no increase, increased mortality, significant decrease, subgroup analysis, decrease, Result, significantly, evaluated, required, searched, contribute, hospitalized patient, demonstrated, baseline, eligible, patients with COVID-19, retrieved, the cytokine storm, with COVID-19, 【제목키워드】 review, Safety, janus, kinase,